The genome and transcriptome of the zoonotic hookworm Ancylostoma ceylanicum identify infection-specific gene families

Abstract

Hookworms infect over 400 million people, stunting and impoverishing them1–3. Sequencing hookworm genomes and finding which genes they express during infection should help in devising new drugs or vaccines against hookworms4,5. Unlike other hookworms, Ancylostoma ceylanicum infects both humans and other mammals, providing a laboratory model for hookworm disease6,7. We determined an A. ceylanicum genome sequence of 313 Mb, with transcriptomic data throughout infection showing expression of 30,738 genes. Approximately 900 genes were upregulated during early infection in vivo, including ASPRs, a cryptic subfamily of activation-associated secreted proteins (ASPs)8. Genes downregulated during early infection included ion channels and G protein–coupled receptors; this downregulation was observed in both parasitic and free-living nematodes. Later, at the onset of heavy blood feeding, C-lectin genes were upregulated along with genes for secreted clade V proteins (SCVPs), encoding a previously undescribed protein family. These findings provide new drug and vaccine targets and should help elucidate hookworm pathogenesis.

The genomic basis of nematode parasitism

“…The expansion of this gene family in Strongyloides also chimes with analyses of genomes of other species [13]. For example, the hookworms Ancylostoma ceylanicum and Necator americanus have 432 and 137 of these genes [32,33], and H. contortus 161, compared with 36 in the free-living species C. elegans (and as a further comparison, there are 33 in Pristionchus pacifiicus, which lives in close association with beetles, but does not appear to be a parasite [34]). This gene family is also reported to be expanded in another clade V nematode, D. viviparus [30].…”

The barber's pole worm CAP protein superfamily — A basis for fundamental discovery and biotechnology advances

“…americanus (cf. Hawdon et al, 1996, 1999;Datu et al, 2008;Tang et al, 2014;Schwarz et al, 2015), but contrasts with the small numbers of homologous genes inferred from transcriptomic and genomic sequence data sets for some other nematodes studied to date, including Ascaris suum, Toxocara canis and Trichuris suis (see Jex et al, 2011Jex et al, , 2014Zhu et al, 2015). The reason(s) for this apparent difference is unclear, but could relate to differences in developmental and reproductive biology as well as varying modes of host invasion and immune modulation or evasion among nematode species (cf.…”

“…1B), initially suggesting that these molecules play key roles in the infection process and/or in maintaining the parasite-host relationship. Although no direct comparison was undertaken here, this upregulation appears to be distinct from hookworms A. caninum, A. ceylanicum and N. americanus (see Goud et al, 2005;Datu et al, 2008;Osman 2012;Schwarz et al, 2015), which usually undergo percutaneous, pulmonary and/or somatic migration, and establish in the small intestine rather than the abomasum. This latter difference could explain the apparent expansions of CAP protein genes in N. americanus (n = 128; Tang et al, 2014) and A. ceylanicum (n = 432; Schwarz et al, 2015) compared with H. contortus.…”

“…Although no direct comparison was undertaken here, this upregulation appears to be distinct from hookworms A. caninum, A. ceylanicum and N. americanus (see Goud et al, 2005;Datu et al, 2008;Osman 2012;Schwarz et al, 2015), which usually undergo percutaneous, pulmonary and/or somatic migration, and establish in the small intestine rather than the abomasum. This latter difference could explain the apparent expansions of CAP protein genes in N. americanus (n = 128; Tang et al, 2014) and A. ceylanicum (n = 432; Schwarz et al, 2015) compared with H. contortus. The relatively high proportion (28%) of CAP molecules of H. contortus with homologues in C. elegans contrasts with the situation for N. americanus and A. ceylanicum (see Tang et al, 2014;Schwarz et al, 2015), in which only six of 137 (4.3%) CAP proteins have orthologues in the free-living nematode.…”

“…This latter difference could explain the apparent expansions of CAP protein genes in N. americanus (n = 128; Tang et al, 2014) and A. ceylanicum (n = 432; Schwarz et al, 2015) compared with H. contortus. The relatively high proportion (28%) of CAP molecules of H. contortus with homologues in C. elegans contrasts with the situation for N. americanus and A. ceylanicum (see Tang et al, 2014;Schwarz et al, 2015), in which only six of 137 (4.3%) CAP proteins have orthologues in the free-living nematode. In addition, there are five paralogs encoding related proteins in H. contortus, which further suggests that they relate to parasite-specific functions.…”